The case for the therapeutic use of mechanistic/mammalian target of rapamycin (mTOR) inhibitors in xenotransplantation

Abstract

AbstractThe mechanistic/mammalian target of rapamycin (mTOR) is one of the systems that are necessary to maintain cell homeostasis, such as survival, proliferation, and differentiation. mTOR inhibitors (mTOR‐Is) are utilized as immunosuppressants and anti‐cancer drugs. In organ allotransplantation, current regimens infrequently include an mTOR‐I, which are positioned more commonly as alternative immunosuppressants. In clinical allotransplantation, long‐term efficacy has been established, but there is a significant incidence of adverse events, for example, inhibition of wound healing, buccal ulceration, anemia, hyperglycemia, dyslipidemia, and thrombocytopenia, some of which are dose‐dependent. mTOR‐Is have properties that may be especially beneficial in xenotransplantation. These include suppression of T cell proliferation, increases in the number of T regulatory cells, inhibition of pig graft growth, and anti‐inflammatory, anti‐viral, and anti‐cancer effects. We here review the potential benefits and risks of mTOR‐Is in xenotransplantation and suggest that the benefits exceed the adverse effects.